Medical devices having improved performance

ABSTRACT

In accordance with various aspects of the invention, implantable and insertable medical devices are provided, which contain one or more polymeric regions. In one aspect, the polymeric regions comprise (a) a block copolymer that comprises a polyaromatic block and a polyalkene block admixed with (b) a sulfonated high Tg polymer. In another aspect, the polymeric regions comprise a block copolymer that comprises (a) a sulfonated polymer block and (b) fluorinated polymer block.

STATEMENT OF RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.11/714,029, filed Mar. 5, 2007, which is incorporated by referenceherein in its entirety.

FIELD OF THE INVENTION

The present invention relates generally to medical devices, and moreparticularly to implantable or insertable medical devices.

BACKGROUND OF THE INVENTION

The implantation or insertion of medical devices into the body of apatient is common in the practice of modern medicine. For instance, inthe past ten years stents have emerged as a prime therapy forarthroclerosis because they counteract the effects of intimalhyperplasia from balloon injury. Unfortunately, in-stent restenosis is adisease that may occur from the injury to the vessel wall. Drug elutingstents have a polymeric coating over the stent to release a drug at aprescribed rate for a given duration to counteract the effects ofin-stent restenosis. The coating on the stent is in contact with thedelivery system (e.g., balloon) along its inner diameter and in contactwith the vessel wall along its outer diameter. It is advantageous tooptimize the properties of the polymeric coating so as to control therelease of drug, have optimum biocompatibility against the vessel wall,and be mechanically compatible with the surface of the balloon. Examplesof drug eluting coronary stents include commercially available stentsfrom Boston Scientific Corp. (TAXUS), Johnson & Johnson (CYPHER), andothers. See S. V. Ranade et al., Acta Biomater. 2005 January; 1(1):137-44 and R. Virmani et al., Circulation 2004 Feb. 17, 109(6) 701-5.

Various types of polymeric materials have been used as drug-releasingreservoirs, including, for example, homopolymers such as poly(n-butylmethacrylate) and copolymers such as poly(ethylene-co-vinyl acetate) andpoly(isobutylene-co-styrene), for example,poly(styrene-b-isobutylene-b-styrene) triblock copolymers (SIBS), whichare described, for instance, in U.S. Pat. No. 6,545,097 to Pinchuk etal. SIBS triblock copolymers have a soft, elastomeric low glasstransition temperature (Tg) midblock and hard elevated Tg endblocks. Aswith many block copolymers, SIBS tends to phase separate, with theelastomeric blocks aggregating to form elastomeric phase domains and thehard blocks aggregating to form hard phase domains. It has beenhypothesized that, because each elastomeric block has a hard block ateach end, and because different hard blocks within the same triblockcopolymer are capable of occupying two different hard phase domains, thehard phase domains become physically crosslinked to one another via theelastomeric blocks. Moreover, because the crosslinks are not covalent innature, they can be reversed, for example, by dissolving or melting theblock copolymer. Consequently, SIBS copolymers are thermoplasticelastomers, in other words, elastomeric (i.e., reversibly deformable)polymers that form physical crosslinks which can be reversed by meltingthe polymer (or, in the case of SIBS, by dissolving the polymer in asuitable solvent).

SUMMARY OF THE INVENTION

In accordance with various aspects of the invention, implantable andinsertable medical devices are provided, which contain one or moreblock-copolymer-containing polymeric regions.

In a first aspect, the polymeric regions comprise (a) a block copolymerthat comprises a polyaromatic block and a polyalkene block admixed with(b) a sulfonated high Tg polymer.

In a second aspect, the polymeric regions comprise a block copolymerthat comprises (a) a sulfonated polymer block and (b) fluorinatedpolymer block.

An advantage of the present invention is that a variety of physical andchemical characteristics may be tailored for a given polymeric region,including one or more of the following, among others: biocompatibility,surface tack, elasticity, water diffusivity, therapeutic agentdiffusivity (where a therapeutic agent is present), andhydrophobic/hydrophilic balance (influencing, for example, wettability,as well as water diffusivity and therapeutic agent diffusivity, where atherapeutic agent is present).

These and other aspects, embodiments and advantages of the presentinvention will become immediately apparent to those of ordinary skill inthe art upon review of the Detailed Description and Claims to follow.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a bar graph depicting surface tack of 30 mol % SIBS in bothsulfonated and non-sulfonated forms.

DETAILED DESCRIPTION OF THE INVENTION

A more complete understanding of the present invention is available byreference to the following detailed description of numerous aspects andembodiments of the invention. The detailed description of the inventionwhich follows is intended to illustrate but not limit the invention.

In accordance with various aspects of the invention, implantable andinsertable medical devices are provided, which contain one or moreblock-copolymer-containing polymeric regions (e.g., an entire medicaldevice, one or more portions of a medical device, etc.).

In a first aspect, the polymeric regions comprise (a) a block copolymerthat comprises a polyaromatic block and a polyalkene block admixed with(a) a sulfonated high Tg polymer.

SIBS is one example of a block copolymer of this type, among manyothers. As noted above, SIBS copolymers are useful in drug-releasingcoronary stent coatings. In addition to its ability to serve as a drugdelivery reservoir, SIBS has excellent biocompatibility, elasticity,strength, and processability. Where a SIBS coating is deployed on astent, the coating on the inner diameter of the stent is typically incontact with the delivery system (e.g., a balloon) and subsequently thebloodstream, whereas the coating on the outer diameter is deployedagainst the body lumen wall (e.g., a blood vessel wall). In this regard,surface coatings of sulfonated copolymers (e.g., sulfonated PEO) havebeen shown to have anti-thrombogenic effects in vivo as measured by areduction of platelet and vascular smooth muscle cell adhesion. See,e.g., H. J. Lee et. al., J. Biomater. Sci. Polymer Edn., Vol. 13, No. 8,pp. 939-952 (2002). While sulfonated SIBS has elastomeric and substrateadhesion properties desired for a conformal or abluminal stent coating,as seen from FIG. 1, this material has increased surface tack comparedto non-sulfonated SIBS with comparable styrene levels (30 mol %).Surface tack is an important property for stent coatings, as highsurface tack can cause defects in the coating after the stent isexpanded/deployed. The non-sulfonated SIBS in FIG. 1 was formed bycationic polymerization along the lines described in U.S. Pat. No.6,545,097 to Pinchuk et al. To create the sulfonated form, this polymerwas sulfonated along the lines described in Z. Shi et al.,Macromolecules 2005, 38, 4193-4201.

Thus, accordance with the above-described first aspect of the invention,the polymeric region is supplied with sulfonate groups, not bysulfonating the block copolymer, but rather by supplying sulfonategroups in conjunction with a distinct polymer, specifically, asulfonated high Tg polymer.

In a second aspect of the invention, on the other hand, the polymericregion is supplied with sulfonate groups by including them within ablock copolymer that comprises (a) a sulfonated polymer block and (b)fluorinated polymer block. As is well known, fluorinated polymer blockstypically have inherently surface energies (and thus low surface tack),relative to various other polymer blocks, including polyalkene polymerblocks such as polyisobutylene.

Examples of medical devices for the practice of the present inventioninclude implantable or insertable medical devices, for example, stents(including coronary vascular stents, peripheral vascular stents,cerebral, urethral, ureteral, biliary, tracheal, gastrointestinal andesophageal stents), stent coverings, stent grafts, vascular grafts,valves including heart valves and vascular valves, abdominal aorticaneurysm (AAA) devices (e.g., AAA stents, AAA grafts, etc.), vascularaccess ports, dialysis ports, embolization devices including cerebralaneurysm filler coils (including Guglilmi detachable coils and metalcoils), embolic agents, tissue bulking devices, catheters (e.g., renalor vascular catheters such as balloon catheters and various centralvenous catheters), guide wires, balloons, filters (e.g., vena cavafilters and mesh filters for distil protection devices), septal defectclosure devices, myocardial plugs, patches, pacemakers, lead coatingsincluding coatings for pacemaker leads, defibrillation leads and coils,ventricular assist devices including left ventricular assist hearts andpumps, total artificial hearts, shunts, anastomosis clips and rings,cochlear implants, and tissue engineering scaffolds for cartilage, bone,skin and other in vivo tissue regeneration, urethral slings, hernia“meshes”, artificial ligaments, orthopedic prosthesis, dental implants,biopsy devices, as well as any coated substrate (which can comprise, forexample, metals, polymers, ceramics and combinations thereof) that isimplanted or inserted into the body.

In some embodiments, the polymeric regions of the present inventioncorrespond to an entire medical device. In other embodiments, thepolymeric regions correspond to one or more portions of a medicaldevice. For instance, the polymeric regions can be in the form ofmedical device components, in the form of one or more fibers which areincorporated into a medical device, in the form of one or more polymericlayers formed over all or only a portion of an underlying substrate, andso forth. Materials for use as underlying medical device substratesinclude ceramic, metallic and polymeric substrates. The substratematerial can also be a carbon- or silicon-based material, among others.Layers can be provided over an underlying substrate at a variety oflocations and in a variety of shapes (e.g., in the form of a series ofrectangles, stripes, or any other continuous or non-continuous pattern).As used herein a “layer” of a given material is a region of thatmaterial whose thickness is small compared to both its length and width.As used herein a layer need not be planar, for example, taking on thecontours of an underlying substrate. Layers can be discontinuous (e.g.,patterned).

As used herein, a “polymeric region” is a region (e.g., an entiredevice, a device component, a device coating layer, etc.) that containspolymers, for example, from 50 wt % or less to 75 wt % to 90 wt % to 95wt % to 97.5 wt % to 99 wt % or more polymers.

As used herein, “polymers” are molecules containing multiple copies(e.g., from 5 to 10 to 25 to 50 to 100 to 250 to 500 to 1000 or morecopies) of one or more constitutional units, commonly referred to asmonomers. As used herein, the term “monomers” may refer to the freemonomers and to those that have been incorporated into polymers, withthe distinction being clear from the context in which the term is used.

Polymers may take on a number of configurations, which may be selected,for example, from linear, cyclic and branched configurations, amongothers. Branched configurations include star-shaped configurations(e.g., configurations in which three or more chains emanate from asingle branch point), comb configurations (e.g., configurations having amain chain and a plurality of side chains, also referred to as “graft”configurations), dendritic configurations (e.g., arborescent andhyperbranched polymers), and so forth.

As used herein, “homopolymers” are polymers that contain multiple copiesof a single constitutional unit (i.e., monomer). “Copolymers” arepolymers that contain multiple copies of at least two dissimilarconstitutional units, examples of which include random, statistical,gradient, periodic (e.g., alternating) and block copolymers.

As used herein, “block copolymers” are copolymers that contain two ormore polymer blocks that differ in composition, for instance, because aconstitutional unit (i.e., monomer) is found in one polymer block thatis not found in another polymer block. As used herein, a “polymer block”or “block” is a grouping of constitutional units (e.g., 5 to 10 to 25 to50 to 100 to 250 to 500 to 1000 or more units). Blocks can be unbranchedor branched. Blocks can contain a single type of constitutional unit(also referred to herein as “homopolymeric blocks”) or multiple types ofconstitutional units (also referred to herein as “copolymeric blocks”)which may be present, for example, in a random, statistical, gradient,or periodic (e.g., alternating) distribution.

As used herein, a “chain” is a linear polymer or a portion thereof, forexample, a linear block.

Polymers and polymer blocks for use in the present invention include lowglass transition temperature (Tg) polymers and polymer blocks and highTg polymers and polymer blocks. As used herein, a “low Tg polymer” or a“low Tg polymer block” is one that displays a Tg that is below bodytemperature, more typically from 35° C. to 20° C. to 0° C. to −25° C. to−50° C. or below. Conversely, as used herein, a “high Tg polymer” or a“high Tg polymer block” is one that displays a Tg that is above bodytemperature, more typically from 40° C. to 50° C. to 75° C. to 100° C.or above. Tg can be measured by differential scanning calorimetry (DSC).

As noted above, in accordance with various aspects of the invention,medical devices are provided, which contain one or more polymericregions. In one aspect, the polymeric regions comprise a block copolymerthat comprises (a) a sulfonated polymer block and (b) a fluorinatedpolymer block.

Fluorinated monomers for use in forming the fluorinated polymer blocksmay be selected from one or more suitable members of the following,among others (some of which are presented with a published Tg for thehomopolymer): (a) partially and fully fluorinated alkene monomers (whichconsist of carbon, fluorine and optionally hydrogen), such as vinylfluoride (Tg 40° C.), vinylidene fluoride (Tg −40° C.),trifluoroethylene, tetrafluoroethylene, and hexafluoropropylene, (b)partially and fully halogenated alkene monomers having fluorine andchlorine substitution (which consist of carbon, fluorine, chlorine andoptionally hydrogen) such as chlorotrifluoroethylene, (c) fluorinatedesters including acrylate esters with partially and fully fluorinatedalkyl groups such as 2,2,2-trifluoroethyl acrylate (Tg −10° C.) andpentafluoroethyl acrylate, methacrylate esters with partially and fullyfluorinated alkyl groups such as 2,2,2-trifluoroethyl methacrylate andpentafluoroethyl methacrylate, and vinyl esters with partially and fullyfluorinated alkyl groups such as vinyl trifluoroacetate (Tg 46° C.), (d)vinyl ethers with partially and fully fluorinated alkyl groups such asperfluoromethyl vinyl ether, perfluoroethyl vinyl ether andperfluoropropyl vinyl ether.

Sulfonated polymer blocks include those that are formed by polymerizingsulfonated monomers and those that are sulfonated after the monomershave been incorporated by polymerization. Thus, sulfonated monomersinclude those that are sulfonated at the time of monomer incorporation(polymerization) and those that are formed after monomer incorporation.

Examples of the former include vinyl sulfonic acid, styrene sulfonicacid, allyl sulfonic acid, sulfoethyl methacrylate, sulfopropylmethacrylate, 2-acrylamido-2-methylpropane sulfonic acid (AMPS),1-allyloxy-2-hydroxypropane sulfonic acid, and3-allyloxy-2-hydroxypropane sulfonic acid, among others, as well assalts thereof, including ammonium, alkali metal (e.g., Li, Na, K, etc.)and alkaline earth metal (Be, Mg, Ca, etc.) salts, among others.

Examples of the latter include readily sulfonatable monomers such asaromatic monomers, for example, (1) vinyl aromatic monomers such as (a)unsubstituted vinyl aromatics, such as styrene (Tg 100° C.) and 2-vinylnaphthalene (Tg 151° C.), (b) vinyl substituted aromatics such asalpha-methyl styrene, (c) ring-substituted vinyl aromatics includingring-alkylated vinyl aromatics such as 3-methylstyrene (Tg 97° C.),4-methylstyrene (Tg 97° C.), 2,4-dimethylstyrene (Tg 112° C.),2,5-dimethylstyrene (Tg 143° C.), 3,5-dimethylstyrene (Tg 104° C.),2,4,6-trimethylstyrene (Tg 162° C.), and 4-tert-butylstyrene (Tg 127°C.), ring-alkoxylated vinyl aromatics, such as 4-methoxystyrene (Tg 113°C.) and 4-ethoxystyrene (Tg 86° C.), ring-halogenated vinyl aromaticssuch as 2-chlorostyrene (Tg 119° C.), 3-chlorostyrene (Tg 90° C.),4-chlorostyrene (Tg 110° C.), 2,6-dichlorostyrene (Tg 167° C.) and4-bromostyrene (Tg 118° C.), ring-ester-substituted vinyl aromatics suchas 4-acetoxystyrene (Tg 116° C.), ring-hydroxylated vinyl aromatics suchas 4-hydroxystyrene (Tg 174° C.), ring-amino-substituted vinyl aromaticsincluding 4-amino styrene, ring-silyl-substituted styrenes such asp-dimethylethoxy siloxy styrene, (d) unsubstituted and substituted vinylpyridines such as 2-vinyl pyridine (Tg 104° C.) and 4-vinyl pyridine (Tg142° C.), (e) vinyl aromatic esters such as vinyl benzoate (Tg 71° C.)and vinyl 4-tert-butyl benzoate (Tg 101° C.), and (f) other vinylaromatic monomers such as vinyl carbazole (Tg 227° C.) and vinylferrocene (Tg 189° C.), (2) aromatic acrylates such as benzyl acrylate(Tg 6° C.), (3) aromatic methacrylates such as phenyl methacrylate (Tg110° C.) and benzyl methacrylate (Tg 54° C.). For ring substitutedaromatics, the rate and degree of the sulfonation will depend on thenature of the substituents. For example, aromatics with electrondonating groups (e.g., amines, hydroxyls, alkyl, alkoxy, etc.) willtypically react faster than unsubstituted aromatics, whereas aromaticswith electron withdrawing groups (e.g., halogen, nitro, nitrile, etc.)will typically decrease the rate of sulfonation.

Examples of the latter further include diene monomers such as1,3-butadiene, 2-methyl-1,3-butadiene (isoprene),2,3-dimethyl-1,3-butadiene, 2-ethyl-1,3-butadiene, 1,3-pentadiene,2-methyl-1,3-pentadiene, 4-butyl-1,3-pentadiene,2,3-dibutyl-1,3-pentadiene, 2-ethyl-1,3-pentadiene, 1,3-hexadiene,1,3-octadiene, 3-butyl-1,3-octadiene, cis-chlorobutadiene (Tg −20° C.),and trans-chlorobutadiene (Tg −40° C.), among others.

The fluorinated polymer block, the sulfonated polymer block (or itsnon-sulfonated counterpart) may independently be, for example, low orhigh Tg polymer blocks.

For instance, in certain embodiments, the block copolymer may compriseone or more high Tg fluorinated polymer blocks and one or more low Tgsulfonated polymer blocks.

In certain other embodiments, the block copolymer may comprise one ormore low Tg fluorinated polymer blocks and one or more high Tgsulfonated polymer blocks.

For example, in some embodiments, the block copolymer may contain (a)one or more sulfonated polystyrene blocks and (b) one or more low Tgfluorinated polymer blocks selected from a polyvinylidene fluorideblock, a polyhexafluoropropylene block, a poly(vinylidenefluoride-co-hexafluoropropylene) block, apoly(tetrafluoroethylene-co-perfluoromethyl vinyl ether) block, apoly(vinylidene fluoride-co-chlorotrifluoroethylene) block, apoly(tetrafluoroethylene-co-propylene) block, and a poly(vinylidenefluoride-co-hexafluoropropylene-co-tetrafluoroethylene) block, apoly(vinylidene fluoride-co-fluorinated vinylether-co-tetrafluoroethylene) block, a poly(vinylidenefluoride-co-propylene-co-tetrafluoroethylene) block, and apoly(vinylidene fluoride-co-fluorinated vinylether-co-hexafluoropropylene-co-ethylene-co-tetrafluoroethylene) block.

In certain embodiments of the invention, the block copolymer comprisesat least one low Tg block and at least two high Tg blocks, with at leasta portion of a low Tg block separating two high Tg blocks (in otherwords the high Tg blocks are interconnected via a low Tg block).Examples of this architecture include, for example, the followingconfigurations, among many others, in which low Tg polymer blocks aredesignated “L” and high Tg polymer blocks are designated “H”: (a) blockcopolymers having alternating chains of the type HLH, (HL)_(m),L(HL)_(m) and H(LH)_(m) where m is a positive whole number of 2 or more,(b) multiarm (including star) copolymers such as X(LH)_(m), where m is apositive whole number of 2 or more and where X is a hub species (e.g.,an initiator molecule residue, a linking residue, etc.), which istypically ignored in block copolymer terminology, for example, withX(LH)₂ described as a triblock copolymer of the formula HLH and (c) combcopolymers having an L chain backbone and multiple H side chains.Polymers of this type are capable of demonstrating high strength andelastomeric properties, while at the same time being processable usingtechniques such as solvent- and/or melt-based processing techniques.

In another aspect, polymeric regions for medical devices are provided,which comprise (a) a block copolymer that comprises a polyalkene blockand a polyaromatic block admixed with (b) a sulfonated high Tg polymer.

Examples of polyalkene blocks may be selected for example, for one ormore of the following, among others: mono-unsaturated C2-C10 alkenessuch as ethylene, propylene (Tg −8 to −13° C.), isobutylene (Tg −73°C.), 1-butene (Tg −24° C.), 4-methyl pentene (Tg 29° C.), 1-octene (Tg−63° C.) and other α-olefins, and C4-C15 dienes such as 1,3-butadiene,2-methyl-1,3-butadiene (isoprene), 2,3-dimethyl-1,3-butadiene,2-ethyl-1,3-butadiene, 1,3-pentadiene, 2-methyl-1,3-pentadiene,4-butyl-1,3-pentadiene, 2,3-dibutyl-1,3-pentadiene,2-ethyl-1,3-pentadiene, 1,3-hexadiene, 1,3-octadiene, and3-butyl-1,3-octadiene.

Examples of polyaromatic blocks include those formed from one or more ofthe following monomers, among others: (1) vinyl aromatic monomersincluded (a) unsubstituted vinyl aromatics, such as styrene (Tg 100° C.)and 2-vinyl naphthalene (Tg 151° C.), (b) vinyl substituted aromaticssuch as alpha-methyl styrene, (c) ring-substituted vinyl aromaticsincluding ring-alkylated vinyl aromatics such as 3-methylstyrene (Tg 97°C.), 4-methylstyrene (Tg 97° C.), 2,4-dimethylstyrene (Tg 112° C.),2,5-dimethylstyrene (Tg 143° C.), 3,5-dimethylstyrene (Tg 104° C.),2,4,6-trimethylstyrene (Tg 162° C.), and 4-tert-butylstyrene (Tg 127°C.), ring-alkoxylated vinyl aromatics, such as 4-methoxystyrene (Tg 113°C.) and 4-ethoxystyrene (Tg 86° C.), ring-halogenated vinyl aromaticssuch as 2-chlorostyrene (Tg 119° C.), 3-chlorostyrene (Tg 90° C.),4-chlorostyrene (Tg 110° C.), 2,6-dichlorostyrene (Tg 167° C.),4-bromostyrene (Tg 118° C.) and 4-fluorostyrene (Tg 95° C.),ring-ester-substituted vinyl aromatics such as 4-acetoxystyrene (Tg 116°C.), ring-hydroxylated vinyl aromatics such as 4-hydroxystyrene (Tg 174°C.), ring-amino-substituted vinyl aromatics including 4-amino styrene,ring-silyl-substituted styrenes such as p-dimethylethoxy siloxy styrene,(d) unsubstituted and substituted vinyl pyridines such as 2-vinylpyridine (Tg 104° C.) and 4-vinyl pyridine (Tg 142° C.), (e) vinylaromatic esters such as vinyl benzoate (Tg 71° C.) and vinyl4-tert-butyl benzoate (Tg 101° C.), and (f) other vinyl aromaticmonomers such as vinyl carbazole (Tg 227° C.) and vinyl ferrocene (Tg189° C.), (2) aromatic acrylates such as benzyl acrylate (Tg 6° C.) and(3) aromatic methacrylates such as phenyl methacrylate (Tg 110° C.) andbenzyl methacrylate (Tg 54° C.).

Examples of sulfonated high Tg polymers include high Tg sulfonatedhomopolymers and copolymers.

In some embodiments, a sulfonated high Tg homopolymer may be formed bypolymerizing a sulfonated monomer (e.g., a sulfonated aromatic monomersuch as styrene sulfonic acid or a salt thereof). In other embodiments asulfonated high Tg homopolymer may be formed by sulfonating a suitablehomopolymer, for example, an aromatic homopolymer formed from a suitablearomatic monomer (e.g., selected from sulfonatable members of theforgoing aromatic monomers).

In some embodiments, a sulfonated high Tg copolymer may be formed bycopolymerizing (a) a sulfonated monomer (e.g., a sulfonated aromaticmonomer) and (b) one or more comonomers selected from sulfonatedcomonomers, non-sulfonated comonomers (e.g., high Tg non-sulfonatedcomonomers selected from suitable members of those set forth below), orboth. In other embodiments a sulfonated high Tg copolymer may be formedby sulfonating a suitable copolymer, for example, a copolymer thatcomprises (a) a sulfonatable monomer and (b) one or more comonomersselected from sulfonatable comonomers, non-sulfonatable comonomers(e.g., selected from non-sulfonatable members of the high Tg comonomersset forth below), or both.

Clearly, the monomers selected for the above methods should becompatible with the polymerization and/or sulfonation conditions thatare employed.

Examples of non-sulfonated and non-sulfonatable comonomers may beselected from suitable members of the following, among others: (1)unsaturated anhydride monomers such as maleic anhydride, (2) high Tgvinyl monomers including (a) high Tg vinyl aromatics such as those setforth above, (b) high Tg vinyl esters such as vinyl cyclohexanoate (Tg76° C.), vinyl pivalate (Tg 86° C.), vinyl trifluoroacetate (Tg 46° C.),vinyl butyral (Tg 49° C.), (c) high Tg vinyl amines, (d) high Tg vinylhalides such as vinyl chloride (Tg 81° C.) and vinyl fluoride (Tg 40°C.), (e) high Tg alkyl vinyl ethers such as tert-butyl vinyl ether (Tg88° C.) and cyclohexyl vinyl ether (Tg 81° C.), (f) other vinyl monomerssuch as vinyl pyrrolidone; (3) high Tg methacrylic monomers including(a) methacrylic acid anhydride (Tg 159° C.), (b) methacrylic acid esters(methacrylates) including (i) alkyl methacrylates such as methylmethacrylate (Tg 105-120° C.), ethyl methacrylate (Tg 65° C.), isopropylmethacrylate (Tg 81° C.), isobutyl methacrylate (Tg 53° C.), t-butylmethacrylate (Tg 118° C.) and cyclohexyl methacrylate (Tg 92° C.), (ii)hydroxyalkyl methacrylates such as 2-hydroxyethyl methacrylate (Tg 57°C.) and 2-hydroxypropyl methacrylate (Tg 76° C.), (iii) additionalmethacrylates including isobornyl methacrylate (Tg 110° C.) andtrimethylsilyl methacrylate (Tg 68° C.), and (c) other methacrylic-acidderivatives including methacrylonitrile (Tg 120° C.); (4) high Tgacrylic monomers including (a) acrylic acid esters such as tert-butylacrylate (Tg 43-107° C.), hexyl acrylate (Tg 57° C.) and isobornylacrylate (Tg 94° C.) and (b) other acrylic-acid derivatives includingacrylonitrile (Tg 125° C.).

In a specific embodiment, polymeric regions for medical devices areprovided, which comprise (a) a block copolymer that comprises apolyalkene block and a polyaromatic block, for example, SIBS, among manyothers, blended with (b) a high Tg sulfonated polymer, for example,sulfonated polystyrene and/or sulfonated poly(styrene-co-maleicanhydride), among many others.

As will be appreciated by those of ordinary skill in the art, polymersemployed in accordance with the present invention may be synthesizedaccording to known methods, including cationic, anionic, and radicalpolymerization methods, particularly controlled/“living” cationic,anionic and radical polymerizations.

Living free radical polymerizations (also called controlled free radicalpolymerizations) may be employed in various embodiments of theinvention, due to the undemanding nature of radical polymerizations incombination with the power to control polydispersities, architectures,and molecular eights that living processes provide. Monomers capable offree radical polymerization vary widely and may be selected from thefollowing, among many others: vinyl aromatic monomers such assubstituted and unsubstituted styrenes, substituted and unsubstitutedalkenes such as ethylene, propylene, vinyl fluoride, vinylidene fluoridetetrafluoroethylene, trifluorochloroethylene, vinyl chloride, vinylidenechloride, diene monomers such as 1,3-butadiene, isoprene, chloropreneand p-divinylbenzene, acrylic monomers, for example, acrylic acid,acrylamide, acrylonitrile, and acrylate esters such as butyl acrylate,methacrylic monomers, for example, methacrylic acid, methacrylonitrile,and methacrylate esters such as methyl methacrylate, beta-hydroxyethylmethacrylate, beta-dimethylaminoethyl methacrylate and ethylene glycoldimethacrylate, vinyl esters such as vinyl acetate, as well as otherunsaturated monomers including iraconic acid, fumaric acid, maleic acid,N-vinylpyrrolidinone, N-vinylimidazole, andN,N′-methylenebis-acrylamide, among many others.

Specific examples of free radical polymerization processes includemetal-catalyzed atom transfer radical polymerization (ATRP), stablefree-radical polymerization (SFRP), including nitroxide-mediatedprocesses (NMP), and degenerative transfer including reversibleaddition-fragmentation chain transfer (RAFT) processes. These methodsare well-detailed in the literature and are described, for example, inan article by Pyun and Matyjaszewski, “Synthesis of NanocompositeOrganic/Inorganic Hybrid Materials Using Controlled/“Living” RadicalPolymerization,” Chem. Mater., 13:3436-3448 (2001), B. Reeves, “RecentAdvances in Living Free Radical Polymerization,” Nov. 20, 2001.University of Florida, T. Kowalewski et al., “Complex nanostructuredmaterials from segmented copolymers prepared by ATRP,” Eur. Phys. J. E,10, 5-16 (2003).

ATRP is an appealing free radical polymerization technique, as it istolerant of a variety of functional groups (e.g., alcohol, amine, andsulfonate groups, among others) and thus allows for the polymerizationof many monomers. In monomer polymerization via ATRP, radicals arecommonly generated using organic halide initiators and transition-metalcomplexes. Some typical examples of organic halide initiators includealkyl halides, haloesters (e.g., methyl 2-bromopropionate, ethyl2-bromoisobutyrate, etc.) and benzyl halides (e.g., 1-phenylethylbromide, benzyl bromide, etc.). A wide range of transition-metalcomplexes may be employed, including a variety of Ru-, Cu-, Os- andFe-based systems. Examples of monomers that may be used in ATRPpolymerization reactions include various unsaturated monomers such asalkyl methacrylates, alkyl acrylates, hydroxyalkyl methacrylates, vinylesters, vinyl aromatic monomers, acrylamide, methacrylamide,acrylonitrile, and 4-vinylpyridine, among others. In ATRP, at the end ofthe polymerization, the polymer chains are capped with a halogen atomthat can be readily transformed via S_(N)1, S_(N)2 or radical chemistryto provide other functional groups such as amino groups, among manyothers. Functionality can also be introduced into the polymer by othermethods, for example, by employing initiators that contain functionalgroups which do not participate in the radical polymerization process.Examples include initiators with epoxide, azido, amino, hydroxyl, cyano,and allyl groups, among others. In addition, functional groups may bepresent on the monomers themselves.

Radical polymerizations based upon degenerative transfer systemsgenerally employ transfer agents that contain moieties for bothinitiation and transfer, which are generated in the presence ofradicals. Controlled radical polymerizations from degenerative transferreactions have been performed with alkyl iodides, unsaturatedmethacrylate esters and thioesters as the transfer agents, among others.The use of thioesters in the radical polymerization of vinyl monomersresults in a RAFT polymerization. The RAFT process has proven to be aversatile method, capable of polymerizing an extremely broad range ofradical polymerizable monomers, including functional styrenes,acrylates, methacrylates, and vinyl esters, as well as water solublemonomers including ionic species such as sodium2-acrylamido-2-methylpropanesulfonate (AMPS) and sodium3-acrylamido-3-methylbutanoate (AMBA), among many others. Thio endgroupsremaining after RAFT may be removed or displaced by other groups viaradical chemistry.

SFRP polymerizations, including NMP, utilize alkoxyamine initiators andnitroxide persistent radicals to polymerize monomers such as styrenesand acrylates. A widely used nitroxide in the polymerization of styreneis 2,2,6,6-tetramethylpiperidinyloxy (TEMPO), although more recentlydeveloped nitroxides can also polymerize acrylates, acrylamides,1,3-dienes and acrylonitrile based monomers, among others, in acontrolled fashion. The resulting polymers contain terminal alkoxyaminegroups, which may be transformed with radical chemistry. For example,maleic anhydride or maleimide derivatives may be added to thealkoxyamine, allowing the ready introduction of other functional groups.

Using the above and other polymerization techniques, various strategiesmay be employed for forming polymers in accordance with the invention.

Block copolymer may be prepared using various methods known in thepolymerization art. Examples include successive monomer addition (a)from a mono- or di-functional intiator (e.g., for linear AB or ABA typeblock copolymers, respectively) and (b) tri-, quatra-, penta-, etc.functional initiators (e.g., for the formation of star copolymers).

Multiple types of polymerization techniques may be employed to formblock copolymers. For example, radical polymerization techniques may beemployed for block copolymers that contain monomers which are notradically polymerizable. In this regard, macroinitiators may be preparedusing non-free-radical techniques, such as living anionic or cationictechniques by appropriate modification of the end groups of theresulting polymers, for instance, by the introducing at least oneradically transferable atom, such as those found in alkyl halide groupssuch as benzylic halide and α-halo ester groups, among others. Asanother example, functional initiators (which may be protected) may beemployed for a first type of polymerization process, followed bydeprotection/conversion of the functional group(s), as needed, followedby polymerization via a second polymerization process. As anotherexample, two or more previously formed polymers may be covalentlyattached to one another to create a block copolymer.

Comb-shaped block copolymers may be prepared, for example, bycopolymerization of a macromonomer that has a terminal polymerizablegroup (e.g., a vinyl group, etc.) with another monomer (e.g., anothervinyl monomer, etc.). Mixed side chains may be created using twodiffering macromonomers. The density of the side chains may be varied byvarying the ratio of macromonomer to monomer. Comb-shaped copolymers mayalso be formed by growing polymer side chains from a polymer that haspendant functional groups along its length which act as polymerizationinitiators (e.g., alkyl halide groups for ATRP polymerization).Comb-shaped copolymers may further be formed by coupling end functionalpolymer chains with a polymer that has reactive functional groups alongits length.

As noted above, sulfonated polymers for use in the present invention maybe formed, for example, through the polymerization of sulfonatedmonomers and/or by sulfonating a suitable pre-existing polymer. Variousmethods are known for sulfonating polymers, including those witharomatic rings. Several such methods are described in Pub. No. US2004/0081829 to Klier et al. For example, polymers may be sulfonated bycontact with oleum (sulfur trioxide dissolved in sulfuric acid), bycontact with a sulfonating complex comprising the reaction product ofsulfur trioxide, chlorosulfonic acid or fuming sulfuric acid and a lowertrialkyl phosphate or phosphate, or by a method in which sulfuric acidis combined with acetic anhydride followed by the addition of thismixture to a solution of the polymer in a chlorinated solvent. Salts ofthe resulting polymer may be prepared by reacting the polymer with aneutralizing agent or base (e.g., ammonia, alkylamine, ammoniumhydroxide, sodium hydroxide, potassium hydroxide, etc.). For furtherinformation on these techniques see Pub. No. US 2004/0081829 and thereferences cited therein.

A specific procedure in which the styrenic monomers of SIBS aresulfonated to varying degrees (i.e., 13 to 82 mol % of the styrene) isset forth in Y. A. Elabd et al., Polymer 45 (2004) 3037-3043. Briefly, asolution of SIBS in methylene chloride was stirred and refluxed while aspecified amount of acetyl sulfate in methylene chloride was slowlyadded to begin the sulfonation reaction. The acetyl sulfate in methylenechloride was prepared by adding acetic anhydride and sulfuric acid tochilled methylene chloride while stirring. Acetic anhydride reacts withsulfuric acid to form acetyl sulfate (which acts as the sulfonatingagent) and acetic acid (a by product) and it removes excess water,thereby creating anhydrous conditions for sulfonation. The sulfonationreaction produces sulfonic acid groups which are generally substitutedat the para position of the aromatic ring in the styrene block of thepolymer.

In addition to one or more polymers, the polymeric regions for use inthe medical devices of the present invention may optionally contain oneor more therapeutic agents. “Therapeutic agents,” “drugs,”“pharmaceutically active agents,” “pharmaceutically active materials,”and other related terms may be used interchangeably herein.

The rate of release of therapeutic agent(s) from polymeric regions inaccordance with the invention with depend, for example, on nature of thetherapeutic agents(s), the nature of the polymer(s) (e.g., molecularweight, architecture, and monomer composition) within the polymericregions, and the nature any other optional supplemental species. Forinstance, the nature of the therapeutic agents(s) (e.g.,hydrophilic/hydrophobic) and the nature of the polymers (e.g.,hydrophilic/hydrophobic/swellable) will have a significant effect uponthe release of the drug (affecting, for example, the wettability of thepolymeric regions, the water diffusivity, the therapeutic agentdiffusivity, and so forth). The hydrophilic/hydrophobic/swellable natureof the polymeric region may also be modified by optionally addingsupplemental hydrophobic and/or hydrophilic polymers to the polymericregion.

The therapeutic agent release profile may be controlled by other factorssuch as the size, number and/or position of the polymeric regions withinthe device. For example, the release profile of polymeric regions inaccordance with the present invention may be modified by varying thethickness and/or surface areas of the same. Moreover, multiple polymericregions may be employed to modify the release profile. For example,polymeric regions, either having the same or different content (e.g.,different polymeric and/or therapeutic agent content), may be stacked ontop of one another, may be positioned laterally with respect to oneanother, and so forth. Moreover, polymeric barrier layers may beprovided over the therapeutic-agent-containing polymeric regions asdescribed herein, or the polymeric regions described herein may bedisposed over therapeutic agent containing regions as barrier layers.

A wide variety of therapeutic agents can be employed in conjunction withthe present invention including those used for the treatment of a widevariety of diseases and conditions (i.e., the prevention of a disease orcondition, the reduction or elimination of symptoms associated with adisease or condition, or the substantial or complete elimination of adisease or condition).

Exemplary therapeutic agents for use in conjunction with the presentinvention include the following: (a) anti-thrombotic agents such asheparin, heparin derivatives, urokinase, clopidogrel, and PPack(dextrophenylalanine proline arginine chloromethylketone); (b)anti-inflammatory agents such as dexamethasone, prednisolone,corticosterone, budesonide, estrogen, sulfasalazine and mesalamine; (c)antineoplastic/antiproliferative/anti-miotic agents such as paclitaxel,5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones,endostatin, angiostatin, angiopeptin, monoclonal antibodies capable ofblocking smooth muscle cell proliferation, and thymidine kinaseinhibitors; (d) anesthetic agents such as lidocaine, bupivacaine andropivacaine; (e) anti-coagulants such as D-Phe-Pro-Arg chloromethylketone, an RGD peptide-containing compound, heparin, hirudin,antithrombin compounds, platelet receptor antagonists, anti-thrombinantibodies, anti-platelet receptor antibodies, aspirin, prostaglandininhibitors, platelet inhibitors and tick antiplatelet peptides; (f)vascular cell growth promoters such as growth factors, transcriptionalactivators, and translational promotors; (g) vascular cell growthinhibitors such as growth factor inhibitors, growth factor receptorantagonists, transcriptional repressors, translational repressors,replication inhibitors, inhibitory antibodies, antibodies directedagainst growth factors, bifunctional molecules consisting of a growthfactor and a cytotoxin, bifunctional molecules consisting of an antibodyand a cytotoxin; (h) protein kinase and tyrosine kinase inhibitors(e.g., tyrphostins, genistein, quinoxalines); (i) prostacyclin analogs;(j) cholesterol-lowering agents; (k) angiopoietins; (l) antimicrobialagents such as triclosan, cephalosporins, aminoglycosides andnitrofurantoin; (m) cytotoxic agents, cytostatic agents and cellproliferation affectors; (n) vasodilating agents; (o) agents thatinterfere with endogenous vasoactive mechanisms; (p) inhibitors ofleukocyte recruitment, such as monoclonal antibodies; (q) cytokines; (r)hormones; (s) inhibitors of HSP 90 protein (i.e., Heat Shock Protein,which is a molecular chaperone or housekeeping protein and is needed forthe stability and function of other client proteins/signal transductionproteins responsible for growth and survival of cells) includinggeldanamycin, (t) alpha receptor antagonist (such as doxazosin,Tamsulosin) and beta receptor agonists (such as dobutamine, salmeterol),beta receptor antagonist (such as atenolol, metaprolol, butoxamine),angiotensin-II receptor antagonists (such as losartan, valsartan,irbesartan, candesartan and telmisartan), and antispasmodic drugs (suchas oxybutynin chloride, flavoxate, tolterodine, hyoscyamine sulfate,diclomine) (u) bARKct inhibitors, (v) phospholamban inhibitors, (w)Serca 2 gene/protein, (x) immune response modifiers includingaminoquizolines, for instance, imidazoquinolines such as resiquimod andimiquimod, and (y) human apolioproteins (e.g., AI, AII, AIII, AIV, AV,etc.).

Numerous therapeutic agents, not necessarily exclusive of those listedabove, have been identified as candidates for vascular treatmentregimens, for example, as agents targeting restenosis. Such agents areuseful for the practice of the present invention and include one or moreof the following: (a) Ca-channel blockers including benzothiazapinessuch as diltiazem and clentiazem, dihydropyridines such as nifedipine,amlodipine and nicardapine, and phenylalkylamines such as verapamil, (b)serotonin pathway modulators including: 5-HT antagonists such asketanserin and naftidrofuryl, as well as 5-HT uptake inhibitors such asfluoxetine, (c) cyclic nucleotide pathway agents includingphosphodiesterase inhibitors such as cilostazole and dipyridamole,adenylate/Guanylate cyclase stimulants such as forskolin, as well asadenosine analogs, (d) catecholamine modulators including α-antagonistssuch as prazosin and bunazosine, β-antagonists such as propranolol andα/β-antagonists such as labetalol and carvedilol, (e) endothelinreceptor antagonists, (f) nitric oxide donors/releasing moleculesincluding organic nitrates/nitrites such as nitroglycerin, isosorbidedinitrate and amyl nitrite, inorganic nitroso compounds such as sodiumnitroprusside, sydnonimines such as molsidomine and linsidomine,nonoates such as diazenium diolates and NO adducts of alkanediamines,S-nitroso compounds including low molecular weight compounds (e.g.,S-nitroso derivatives of captopril, glutathione and N-acetylpenicillamine) and high molecular weight compounds (e.g., S-nitrosoderivatives of proteins, peptides, oligosaccharides, polysaccharides,synthetic polymers/oligomers and natural polymers/oligomers), as well asC-nitroso-compounds, O-nitroso-compounds, N-nitroso-compounds andL-arginine, (g) ACE inhibitors such as cilazapril, fosinopril andenalapril, (h) ATII-receptor antagonists such as saralasin and losartin,(i) platelet adhesion inhibitors such as albumin and polyethylene oxide,(j) platelet aggregation inhibitors including cilostazole, aspirin andthienopyridine (ticlopidine, clopidogrel) and GP IIb/IIIa inhibitorssuch as abciximab, epitifibatide and tirofiban, (k) coagulation pathwaymodulators including heparinoids such as heparin, low molecular weightheparin, dextran sulfate and β-cyclodextrin tetradecasulfate, thrombininhibitors such as hirudin, hirulog,PPACK(D-phe-L-propyl-L-arg-chloromethylketone) and argatroban, FXainhibitors such as antistatin and TAP (tick anticoagulant peptide),Vitamin K inhibitors such as warfarin, as well as activated protein C,(l) cyclooxygenase pathway inhibitors such as aspirin, ibuprofen,flurbiprofen, indomethacin and sulfinpyrazone, (m) natural and syntheticcorticosteroids such as dexamethasone, prednisolone, methprednisoloneand hydrocortisone, (n) lipoxygenase pathway inhibitors such asnordihydroguairetic acid and caffeic acid, (o) leukotriene receptorantagonists, (p) antagonists of E- and P-selectins, (q) inhibitors ofVCAM-1 and ICAM-1 interactions, (r) prostaglandins and analogs thereofincluding prostaglandins such as PGE1 and PGI2 and prostacyclin analogssuch as ciprostene, epoprostenol, carbacyclin, iloprost and beraprost,(s) macrophage activation preventers including bisphosphonates, (t)HMG-CoA reductase inhibitors such as lovastatin, pravastatin,fluvastatin, simvastatin and cerivastatin, (u) fish oils andomega-3-fatty acids, (v) free-radical scavengers/antioxidants such asprobucol, vitamins C and E, ebselen, trans-retinoic acid and SOD mimics,(w) agents affecting various growth factors including FGF pathway agentssuch as bFGF antibodies and chimeric fusion proteins, PDGF receptorantagonists such as trapidil, IGF pathway agents including somatostatinanalogs such as angiopeptin and ocreotide, TGF-β pathway agents such aspolyanionic agents (heparin, fucoidin), decorin, and TGF-β antibodies,EGF pathway agents such as EGF antibodies, receptor antagonists andchimeric fusion proteins, TNF-α pathway agents such as thalidomide andanalogs thereof, Thromboxane A2 (TXA2) pathway modulators such assulotroban, vapiprost, dazoxiben and ridogrel, as well as proteintyrosine kinase inhibitors such as tyrphostin, genistein and quinoxalinederivatives, (x) MMP pathway inhibitors such as marimastat, ilomastatand metastat, (y) cell motility inhibitors such as cytochalasin B, (z)antiproliferative/antineoplastic agents including antimetabolites suchas purine analogs (e.g., 6-mercaptopurine or cladribine, which is achlorinated purine nucleoside analog), pyrimidine analogs (e.g.,cytarabine and 5-fluorouracil) and methotrexate, nitrogen mustards,alkyl sulfonates, ethylenimines, antibiotics (e.g., daunorubicin,doxorubicin), nitrosoureas, cisplatin, agents affecting microtubuledynamics (e.g., vinblastine, vincristine, colchicine, Epo D, paclitaxeland epothilone), caspase activators, proteasome inhibitors, angiogenesisinhibitors (e.g., endostatin, angiostatin and squalamine), rapamycin(sirolimus) and its analogs (e.g., everolimus, tacrolimus, zotarolimus,etc.), cerivastatin, flavopiridol and suramin, (aa) matrixdeposition/organization pathway inhibitors such as halofuginone or otherquinazolinone derivatives and tranilast, (bb) endothelializationfacilitators such as VEGF and RGD peptide, and (cc) blood rheologymodulators such as pentoxifylline.

Preferred therapeutic agents include taxanes such as paclitaxel(including particulate forms thereof, for instance, protein-boundpaclitaxel particles such as albumin-bound paclitaxel nanoparticles,e.g., ABRAXANE), sirolimus, everolimus, tacrolimus, zotarolimus, Epo D,dexamethasone, estradiol, halofuginone, cilostazole, geldanamycin,ABT-578 (Abbott Laboratories), trapidil, liprostin, Actinomcin D,Resten-NG, Ap-17, abciximab, clopidogrel, Ridogrel, beta-blockers,bARKct inhibitors, phospholamban inhibitors, Serca 2 gene/protein,imiquimod, human apolioproteins (e.g., AI-AV), growth factors (e.g.,VEGF-2), as well derivatives of the forgoing, among others.

A wide range of therapeutic agent loadings may be used in conjunctionwith the medical devices of the present invention. Typical loadingsrange, for example, from than 1 wt % or less to 2 wt % to 5 wt % to 10wt % to 25 wt % or more of the polymeric region.

Numerous techniques are available for forming polymeric regions inaccordance with the present invention.

For example, where a polymeric region is formed from one or morepolymers having thermoplastic characteristics, a variety of standardthermoplastic processing techniques may be used to form the polymericregion. Using these techniques, a polymeric region can be formed, forinstance, by (a) first providing a melt that contains polymer(s) and anyother optional agents such as therapeutic agents, and (b) subsequentlycooling the melt. Examples of thermoplastic processing techniquesinclude compression molding, injection molding, blow molding, spraying,vacuum forming and calendaring, extrusion into sheets, fibers, rods,tubes and other cross-sectional profiles of various lengths, andcombinations of these processes. Using these and other thermoplasticprocessing techniques, entire devices or portions thereof can be made.

Other processing techniques besides thermoplastic processing techniquesmay also be used to form the polymeric regions of the present invention,including solvent-based techniques. Using these techniques, polymericregions can be formed, for instance, by (a) first providing a solutionor dispersion that contains polymer(s) and any optional agents such astherapeutic agents and (b) subsequently removing the solvent. Thesolvent that is ultimately selected will contain one or more solventspecies, which are generally selected based on their ability to dissolveat least one of the polymer(s) that form the polymeric region, inaddition to other factors, including drying rate, surface tension, etc.In certain embodiments, the solvent is selected based on its ability todissolve the optional agents, if any. Thus, optional agents such astherapeutic agents may be dissolved or dispersed in the coatingsolution. Preferred solvent-based techniques include, but are notlimited to, solvent casting techniques, spin coating techniques, webcoating techniques, solvent spraying techniques, dipping techniques,techniques involving coating via mechanical suspension including airsuspension, ink jet techniques, electrostatic techniques, andcombinations of these processes.

In some embodiments of the invention, a polymer containing solution(where solvent-based processing is employed) or a polymer containingmelt (where thermoplastic processing is employed) is applied to asubstrate to form a polymeric region. For example, the substrate cancorrespond to all or a portion of an implantable or insertable medicaldevice to which a polymeric coating is applied, for example, byspraying, extrusion, and so forth. The substrate can also be, forexample, a template, such as a mold, from which the polymeric region isremoved after solidification. In other embodiments, for example,extrusion and co-extrusion techniques, one or more polymeric regions areformed without the aid of a substrate. In a specific example, an entiremedical device is extruded. In another, a polymeric coating layer isco-extruded along with and underlying medical device body.

Although various embodiments are specifically illustrated and describedherein, it will be appreciated that modifications and variations of thepresent invention are covered by the above teachings and are within thepurview of the appended claims without departing from the spirit andintended scope of the invention.

1. An implantable or insertable medical device comprising a blockcopolymer that comprises (a) a sulfonated polymer block and (b)fluorinated polymer block.
 2. The medical device of claim 1, wherein thesulfonated polymer block comprises a sulfonated monomer selected fromsulfonated aromatic monomers, sulfonated diene monomers, sulfonatedmethacrylate monomers and combinations thereof.
 3. The medical device ofclaim 1, wherein the sulfonated polymer block comprises a sulfonatedmonomer selected from styrene sulfonic acid, vinyl sulfonic acid, allylsulfonic acid, sulfoalkyl methacrylates, salts thereof, and combinationsthereof.
 4. The medical device of claim 1, wherein the sulfonatedpolymer block is a sulfonated polystyrene block.
 5. The medical deviceof claim 1 wherein the fluorinated polymer block comprises a fluorinatedmonomer selected from partially and fully fluorinated alkene monomers,partially and fully halogenated alkene monomers that comprise fluorineand chlorine substitution, partially and fully fluorinated alkylacrylates, partially and fully fluorinated alkyl methacrylates,partially and fully fluorinated alkyl vinyl esters, partially and fullyfluorinated alkyl vinyl ethers, and combinations thereof.
 6. The medicaldevice of claim 1, wherein the fluorinated polymer block comprises afluorinated monomer selected from vinyl fluoride, vinylidene fluoride,trifluoroethylene, tetrafluoroethylene, hexafluoropropylene,chlorotrifluoroethylene, and combinations thereof.
 7. The medical deviceof claim 1, wherein the fluorinated polymer block is a low Tg block. 8.The medical device of claim 7, wherein the sulfonated polymer block is ahigh Tg polymer block.
 9. The medical device of claim 1, wherein thefluorinated polymer block is a fluorinated elastomeric block selectedfrom a polyvinylidene fluoride block, a polyhexafluoropropylene block,poly(vinylidene fluoride-co-hexafluoropropylene) block, apoly(tetrafluoroethylene-co-perfluoromethyl vinyl ether) block, apoly(vinylidene fluoride-co-chlorotrifluoroethylene) block, apoly(tetrafluoroethylene-co-propylene) block, a poly(vinylidenefluoride-co-hexafluoropropylene-co-tetrafluoroethylene) block, apoly(vinylidene fluoride-co-fluorinated vinylether-co-tetrafluoroethylene) block, a poly(vinylidenefluoride-co-propylene-co-tetrafluoroethylene) block, and apoly(vinylidene fluoride-co-fluorinated vinylether-co-hexafluoropropylene-co-ethylene-co-tetrafluoroethylene) block.10. The medical device of claim 9, wherein the sulfonated polymer blockis a sulfonated polystyrene block.
 11. The medical device of claim 9,wherein the block copolymer is a triblock copolymer comprising saidfluorinated elastomeric block as a mid-block and sulfonated polystyreneblocks as end-blocks. 12-26. (canceled)